Background Behavioral symptoms in individuals with autism spectrum disorder (ASD) have been attributed to abnormal neuronal connectivity, but the molecular bases of these behavioral and brain phenotypes are largely unknown. Human genetic studies have implicated Protocadherin 10 (PCDH10), a member of the δ2 subfamily of non-clustered protocadherin genes, in ASD. PCDH10 expression is enriched in the basolateral amygdala, a brain region implicated in the social deficits of ASD. Previous reports indicate that Pcdh10 plays a role in axon outgrowth and glutamatergic synapse elimination, but its roles in social behaviors and amygdala neuronal connectivity are unknown. We hypothesized that haploinsufficiency of Pcdh10 would reduce social approach behavior and alter the structure and function of amygdala circuits. Methods Mice lacking one copy of Pcdh10 (Pcdh10+/−) and wildtype littermates (WT) were assessed for social approach and other behaviors. The lateral/basolateral amygdala was assessed for dendritic spine number and morphology, and amygdala circuit function was studied using voltage sensitive dye imaging. Expression of Pcdh10 and N-methyl-D-aspartate receptor (NMDAR) subunits was assessed in post-synaptic density fractions of amygdala. Results Male Pcdh10+/− mice have reduced social approach behavior, as well as impaired gamma synchronization, abnormal spine morphology, and reduced levels of NMDAR subunits in amygdala. Social approach deficits in Pcdh10+/− males were rescued with acute treatment with the NMDAR partial agonist d-cycloserine. Conclusions Our studies reveal that male Pcdh10+/− mice have synaptic and behavioral deficits, and establish Pcdh10+/− mice as a novel genetic model for investigating neural circuitry and behavioral changes relevant to ASD.
Objectives/Hypothesis To quantify changes in sleep architecture before and after upper airway stimulation (UAS) therapy in patients with obstructive sleep apnea. Study Design Retrospective chart review. Methods This study was performed at a single‐institution tertiary academic care center. Patients who responded successfully to UAS implantation were selected for this study. Preoperative and postoperative sleep studies were compared to determine sleep architecture changes. Primary outcomes included sleep architecture parameters such as N1, N2, N3, and rapid eye movement (REM) in addition to others. Secondary outcomes included body mass index. Results Thirty‐five patients met inclusion criteria for this study. There was significant improvement across several sleep architecture parameters. N1 sleep percent decreased from 16.7% ± 2.1% preoperatively to 10.1% ± 1.6% postoperatively (P = .023). Time spent in N2 increased from 148.0 ± 12.4 minutes to 185.5 ± 10.4 minutes (P = .030), whereas N3 increased from 21.9 ± 5.0 minutes to 57.0 ± 11.1 minutes (P = .013). No significant changes were observed in REM sleep. Arousal index decreased from 38.8 ± 4.0 to 30.3 ± 4.0 (P = .050). Conclusions There was significant improvement across several sleep architecture parameters among patients who responded successfully to UAS implantation. Level of Evidence 4 Laryngoscope, 130:1085–1089, 2020
Objectives/Hypothesis Hypoglossal nerve stimulation (HNS) has gained increasing interest for the treatment of patients with obstructive sleep apnea (OSA). Drug‐induced sleep endoscopy (DISE) can both exclude improper airway collapse patterns and visualize airway changes under stimulation. Stimulation outcome effects depend on the impulse voltage and electric field resulting from the electrode configuration of the implanted device. The effects of various combinations of voltage and electric field on DISE airway patterns in contrast to awake endoscopy are unknown. Study Design Cohort study. Methods During therapy adjustment about 6 months after implantation, patients underwent a DISE and awake endoscopy with 100% and 125% of functional voltage in three typical electrode configurations (+ – +, o – o, − – −). All videos were analyzed by two separate persons for the opening of the airway at velum, tongue base, and epiglottis level. Results Thirty patients showed typical demographic data. The opening effects were visible in all patients, but there were changes between different electrode configurations. Several demographic or therapeutic aspects such as obesity, OSA severity, or prior soft palate surgery were associated with changes arising from different electrode configurations, but none resulted in a consistently better airway opening. Conclusions In patients with poor results during the therapy adjustment, electric configuration changes can improve airway patency—an independent variable from increasing voltage. As these effects can only be seen in awake endoscopy or DISE, both endoscopies with live stimulation may be considered in cases with insufficient improvement in apnea–hypopnea index after initiation of HNS therapy. Level of Evidence Prospective case series; level 4. Laryngoscope, 131:2148–2153, 2021
Background: A closed suction drain (CSD) is often utilized in head and neck surgical procedures to obliterate dead space. CSDs reduce seroma and hematoma formation, thereby improving skin apposition and wound healing. The use of drains for prolonged periods of time, however, may increase the risk of wound infection. Interestingly, the evidence regarding the need for, and management of, post-operative CSDs after head and neck surgery is scarce. The current criterion of drain removal when output is less than 30 cubic centimeters (cm 3 ) within a 24-hour period and/or on the third post-operative day (POD) is widely utilized. The aforementioned criterion is based on anecdotal evidence from small studies with specific surgical procedures. In this study, we aim to evaluate the criteria for drain removal and to lay the groundwork for an updated paradigm for drain management in head and neck oncologic surgery. Study Design: Retrospective cohort study Setting: Academic tertiary care hospital Methods: A retrospective study was performed. Patients were included if they underwent head and neck surgery at the University of Miami Hospital between January 1, 2019 and July 1, 2020 and had at least one CSD. Volume of drain output on each POD was recorded until the day of drain removal. The development of post-operative wound complications (i.e., seroma, hematoma, infection/abscess, and dehiscence) was also recorded. Results: From our initial cohort of 302 patients, 145 patients met inclusion criteria. A total of 10 patients developed a post-operative wound complication. Patients had a mean age of 58.3 ± 15.0 years. The median inter-quartile range (IQR) drain output (cm 3 ) on the day of CSD removal from patients who developed a wound complication was similar (15; IQR, 5-37.5) when compared to those who did not develop a wound complication (25; IQR, 10-30). This difference was not statistically significant ( p = 0.60). Additionally, the cohort who developed a post-operative wound complication had their drain removed on an earlier POD (1; IQR, 1-1 (Mean 1.2)) when compared to the cohort who did not develop any complications (1; IQR, 1-1 (Mean 1.5)). This difference was also not statistically significant ( p = 0.48) . Conclusion: There is no association between drain output (cm 3 ) or day of CSD removal with the development of wound complications. These results warrant further studies to prospectively evaluate earlier CSD removal in head and neck surgery.
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